Selective Functionalization Of C-H Bond At The 8-Position Of Indolizine

In recent years,the selective functionalization of C-H bonds has attracted much attention in the field of organic chemistry.Due to the similar bond energy and bond strength between C-H bonds,the selective functionalization of C-H bonds is facing a great challenge.Moreover,the activation of C-H bond is a green and efficient synthesis method,which starts from the widely existing C-H bond in nature and avoids the preparation and separation of intermediates.Indolizine compounds have important biological activity and medicinal value,so they are widely used in the fields of biomaterials,medicine,dyes and fluorescent materials.In recent decades,it is not rare to report the functional reactions of C-H bonds on the indene ring at home and abroad,but only limited to the 1 and 3 position C-H bonds on the electronic rich five membered ring of indene,but not on the electronic deficient six membered ring.In this paper,the selective functionalization of the 8-Position C-H bond on the six membered ring of indolizine was studied.A series of 8-alkenylated and aminated indolizine compounds were synthesized with transition metal as catalyst.The research content mainly includes the following two parts:Part I,Alkenylation of C-H bonds at the 8-Position of indolizine.With rhodium as catalyst and copper acetate as oxidant,the alkenylation of 8-Position C-H bond and 2,8-position C-H bond on the indene ring were realized.First of all,the best reaction conditions were obtained through the selection of catalyst type,temperature,solvent and the amount of olefin.In this condition,the application scope of the substrate was extended,and the 8-Position alkylation of indolizine was realized,and the reaction was enlarged to the order of gram.Secondly,we try to deduce the mechanism of this reaction by means of isotope labeling,kinetic experiments and control experiments.Finally,When the 1-ester group is used as the guiding group of indolizine,the ester guiding group can be removed after the alkenylation reaction,and the non trace oriented hydrocarbon activation reaction can be realized.Part II,Amination of C-H bonds at the 8-position of indolizine.A series of 8-amino-indolizine products were obtained by amination of 8-Position C-H bond on indolizine ring with iridium as catalyst.Through the selection of catalyst,temperature,solvent and amine source,the best reaction conditions were obtained,and the range of substrate was extended.